Quantum Sensing Of Mitochondrial Function

线粒体功能的量子传感

• 批准号: BB/T012226/1
• 负责人: Melissa Mather
• 金额: $ 18.79万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT012226%2F1
• 关键词: Quantum; Sensing; Mitochondrial; Function

Mitochondria are small bacteria like organelles contained inside everybody's cells. Often called the battery pack of a cell, they are responsible for taking the oxygen we breathe and using it to generate a molecule known as ATP, the unit of currency for energy production inside most living organisms. Mitochondria generate ATP using chemical reactions that push protons to one side of a small membrane inside the mitochondria. This generates an imbalance of electrical charge across the membrane called mitochondrial membrane potential (MMP), equivalent in strength to the electrical field required for a bolt of lightning to strike during a thunderstorm. This charge imbalance inside the mitochondria pushes protons back through a small protein motor on the membrane to generate ATP, giving cells the energy required to function in their day-to-day tasks. The importance of this little organelle should not be understated and it is widely held to have underpinned the evolution of all complex life on earth. Dysfunctional mitochondria can cause many problems for health and have been linked to a range of diseases such as Parkinson's, heart disease, cancer and obesity. A by-product of this energy creating process in mitochondria are molecules called free radicals. The presence of free radicals inside the body are commonly thought to be a bad thing. It is true that in some circumstances they cause damage to the body however, these free radicals are also involved in many different processes in the body that are vital for the maintenance of health. As such free radicals have to be carefully regulated such that they are not being produced at harmful levels, but in sufficient amounts to allow cells to function normally. Collectively, this balance of free radical production and MMP is referred to as the mitochondrial redox state. This redox state can be a very good indicator of whether a cell is healthy or is undergoing stress or dysfunction. For example, a hallmark of many cancers is 'the Warburg effect' in which cancer cells have a very different mechanism for generating energy which implies a change in the function of mitochondria in growing tumours. Researchers have long been interested in how to better understand mitochondria. However, the technologies we use today have certain limitations; one example is the toxic side effects of different chemicals and invasive probes used to measure MMP. In this work we will develop a new technology that can non-destructively study mitochondria more accurately than existing methods to increase our understanding of these organelles and help develop treatments for diseases more effectively. Our approach is based on a peculiar property of pink diamond that will allow us to use a light microscope to study MMP and free radical production in living cells. Pink diamonds obtain their pinkness due to the presence of Nitrogen impurities lodged in the diamond's usually pure carbon structure. These impurities absorb green light and re-emit red/pink light. Physicists have discovered in the last 10 years that the intensity of this light can be used to measure electromagnetic fields very accurately (~250,000 times smaller than the electric field present in mitochondria) and at very short length scales (about 1 million times smaller than the width of a human hair). Our proposed work involves patterning very thin slabs of diamond with a uniform surface layer of these impurities. Then using a series of controlled pulses of green light, we can take pictures of the red/pink fluorescence using a camera and reconstruct a spatial heat map of electric fields and free radicals produced by mitochondria in cells growing on the diamond surface. We predict this new technology could overcome many of the disadvantages of currently used techniques, and will be able to provide new information about how mitochondria work. This could then lead to new and effective treatments for different diseases for the benefit of all.

线粒体是小细菌，就像每个人细胞内的细胞器。它们通常被称为细胞的电池组，负责吸收我们呼吸的氧气，并利用它产生一种称为ATP的分子，ATP是大多数生物体内能量生产的货币单位。线粒体通过化学反应产生ATP，将质子推到线粒体内小膜的一侧。这会产生一种称为线粒体膜电位（MMP）的跨膜电荷不平衡，其强度相当于雷暴期间闪电击中所需的电场。线粒体内的这种电荷不平衡通过膜上的一个小蛋白质马达将质子推回，以产生ATP，为细胞提供日常工作所需的能量。这个小细胞器的重要性不应该被低估，它被广泛认为是地球上所有复杂生命进化的基础。线粒体功能障碍会导致许多健康问题，并与一系列疾病有关，如帕金森氏症、心脏病、癌症和肥胖症。线粒体中这种能量产生过程的副产品是被称为自由基的分子。体内存在自由基通常被认为是一件坏事。的确，在某些情况下，它们会对身体造成损害，但是，这些自由基也参与了身体中对维持健康至关重要的许多不同过程。因此，必须仔细调节自由基，使其不会以有害水平产生，而是以足够的量使细胞正常运作。总的来说，这种自由基产生和MMP的平衡被称为线粒体氧化还原状态。这种氧化还原状态可以很好地指示细胞是否健康或正在经历压力或功能障碍。例如，许多癌症的一个标志是“瓦尔堡效应”，其中癌细胞具有非常不同的产生能量的机制，这意味着在生长的肿瘤中线粒体功能的改变。长期以来，研究人员一直对如何更好地理解线粒体感兴趣。然而，我们今天使用的技术有一定的局限性;一个例子是用于测量MMP的不同化学品和侵入性探针的毒副作用。在这项工作中，我们将开发一种新技术，可以比现有方法更准确地非破坏性地研究线粒体，以增加我们对这些细胞器的了解，并帮助更有效地开发疾病的治疗方法。我们的方法是基于粉红色钻石的一种特殊性质，这将使我们能够使用光学显微镜来研究活细胞中MMP和自由基的产生。粉红色钻石的粉红色是由于钻石通常是纯碳结构中存在氮杂质。这些杂质吸收绿色光并重新发射红色/粉红色光。物理学家在过去10年中发现，这种光的强度可以用来非常精确地测量电磁场（比线粒体中存在的电场小约25万倍），并且长度尺度非常短（比人类头发的宽度小约100万倍）。我们提出的工作涉及图案非常薄的钻石与这些杂质的均匀表面层。然后使用一系列受控的绿色光脉冲，我们可以使用相机拍摄红色/粉红色荧光的照片，并重建在金刚石表面生长的细胞中线粒体产生的电场和自由基的空间热图。我们预测这项新技术可以克服目前使用的技术的许多缺点，并将能够提供有关线粒体如何工作的新信息。这可能会为所有人带来针对不同疾病的新的有效治疗方法。